Comparable immunogenicity of new modality biotherapeutics delivered subcutaneously or intravenously in non-human primates

Unwanted immunogenicity of therapeutic proteins arises through the combination of many factors, with the route of administration considered a significant contributor. Contrary to historic data on vaccine delivery, analysis of various therapeutic protein products indicates that the subcutaneous route...

Full description

Saved in:
Bibliographic Details
Main Authors: Victoria Koch, Martin Lechmann, Katharine Bray-French, Matthias Füth, Elisabeth Husar, Niels Janssen, Anneliese Schneider, Kay Stubenrauch, Timothy Hickling, Sven Kronenberg
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Journal of Immunotoxicology
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/1547691X.2025.2537408
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Unwanted immunogenicity of therapeutic proteins arises through the combination of many factors, with the route of administration considered a significant contributor. Contrary to historic data on vaccine delivery, analysis of various therapeutic protein products indicates that the subcutaneous route is not a systematic risk. However, individual product assessments may identify factors specific to the circumstance of their use. Preclinical in vivo studies may add additional information to the comparative immunogenicity risk assessment of intravenous versus subcutaneous administrations. Moreover, immunogenicity risk assessment of new biotherapeutic modalities, such as bispecific antibodies and antibody-linked cytokines, may benefit from a full analysis of risk factors, including preclinical in vivo data. The study here provides immunogenicity analysis of an IgG, two CD3 bispecific antibodies, and two Fc-linked immunocytokines administered intravenously and subcutaneously, aiming to highlight similarities and differences between these administration routes. The current results suggest that the development of anti-drug antibodies does not solely depend on the route of administration but is influenced by multiple risk factors, which should be addressed on a case-by-case basis. This paper reflects on the challenges of interpreting the data and propose standards for improving sample and data collection to aid future analysis.
ISSN:1547-691X
1547-6901